Prognostic Value of PD-L1, BAP-1 and ILK in Pleural Mesothelioma

Our plain-English summary of Prognostic Value of PD-L1, BAP-1 and ILK in Pleural Mesothelioma, by O. Illini, M. Benej, A.S. Lang-Stöberl, et al (Journal of Clinical Medicine, 2024).

The study

• Authors: O. Illini, M. Benej, A.S. Lang-Stöberl, H. Fabikan, L. Brcic, F. Sucher, D. Krenbek, T. Krajc, C. Weinlinger, M.J. Hochmair, A. Valipour, T. Klikovits, S. Watzka
• Journal: Journal of Clinical Medicine
• Published: 2024;13(23)
• Cited by: 3 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Pleural mesothelioma (PM) is a rare type of cancer with poor prognosis. Prognostic and predictive biomarkers could improve treatment strategies in these patients. Programmed death ligand 1 (PD-L1), integrin-linked kinase (ILK) and breast cancer gene 1-associated protein (BAP-1) have been proposed to predict outcomes in PM, but existing data are limited and controversial. Design and Methods: This single-center, retrospective study analyzed data on expression patterns and the prognostic role of PD-L1, ILK and BAP-1 in consecutive patients diagnosed with PM. Results: Of all patients (n = 52) included, more than half showed a positive PD-L1 expression (52% TPS ≥ 1%, 65% CPS ≥ 1), 69% showed a BAP-1 loss and 80% an ILK ≥ 50%. Positive PD-L1 expression was more frequent in the non-epithelioid subtype (p = 0.045). ILK intensity (p = 0.032) and positive PD-L1 (p = 0.034) were associated with more advanced tumor stages. The median overall survival (OS) was 16.9 (95% CI 13.1-25.2) months. Multimodality therapy (MMT) including surgery and early stage were independent prognostic factors for longer OS (MMT: HR 0.347, 95% CI 0.13-0.90, p = 0.029; advanced stage: HR 4.989; 95% CI 1.64-15.13, p = 0.005). Patients with an expression of PD-L1 TPS ≥ 1% or BAP-1 positivity showed numerically worse survival with a median OS of 15.3 (11.5; 24.4) vs. 20.0 (11.2; 34.9) and 11.3 (5.6; 31.0) vs. 20.0 (15.2; 28.1) months, respectively. Furthermore, PD-L1 was associated with worse survival in patients receiving MMT (PD-L1 TPS ≥ 1%: 15.8 (12.1-25.4) vs. 31.3 (17.4-95.4) p = 0.053). ILK expression ≥50% did not influence survival. The combinations of CPS ≥ 1% with BAP-1 positivity or ILK expression ≥50% were associated with worse survival (p = 0.045, p = 0.019). Conclusions: In this real-world analysis, expressions of PD-L1 and BAP-1 were associated with worse survival in patients with PM. ILK showed no prognostic value. Further studies with larger cohorts are needed to identify prognostic and predictive biomarkers facilitating optimized individual treatment decision in this rare type of cancer.

In plain English

This retrospective study from one Vienna hospital reviewed 52 patients diagnosed with pleural mesothelioma between 2010 and 2021. The authors compared tumor staining for three markers (PD-L1, BAP-1 and ILK) with survival. The article did not report patients' asbestos exposure. In 51.9% of tumors, PD-L1 was found in at least 1% of tumor cells. BAP-1 was lost in 69.2% of tumors, and 80.4% of 51 tested tumors showed ILK in at least half of tumor cells. Median overall survival was 16.9 months (95% confidence interval 13.1 to 25.2). Only treatment combining surgery with other therapy (longer survival) and late stage (shorter survival) independently predicted survival. Median survival was 15.3 months (11.5 to 24.4) with PD-L1 at that level versus 20.0 months (11.2 to 34.9) below it, and 11.3 months (5.6 to 31.0) for BAP-1-positive patients versus 20.0 months (15.2 to 28.1) with BAP-1 loss. Neither difference was statistically significant. ILK expression was not significantly linked to survival. The authors concluded that patients with PD-L1 expression had survival disadvantages. They cautioned that the small number of patients limits the findings.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Retrospective single-center analysis of patient records and tumor tissue (immunohistochemistry for PD-L1, BAP-1 and ILK)
• Who was studied: 52 patients with histologically confirmed pleural mesothelioma diagnosed between January 2010 and December 2021 at the Clinic Floridsdorf, Vienna, Austria. 78.9% were male, the median age was 70, and 48 had epithelioid, 3 biphasic and 1 sarcomatoid subtype. Stage was known for 37 patients.
• Exposure: Not an asbestos exposure study: the factors studied were tumor expression of PD-L1 (measured as tumor proportion score, TPS, and combined positive score, CPS), BAP-1 and ILK, along with treatment type. Patients' asbestos exposure was not reported.
• Main results:
  • Of all 52 patients, 51.9% had PD-L1 TPS of 1% or more and 65.4% had PD-L1 CPS of 1 or more. 69.2% had BAP-1 loss, and 80.4% (of 51 tested) had ILK in 50% or more of tumor cells.
  • PD-L1 TPS of 1% or more was more frequent in non-epithelioid tumors (p = 0.045; only 4 patients were non-epithelioid) and at late stage (p = 0.034).
  • Weak ILK staining intensity was more often found in late-stage tumors (p = 0.032).
  • Median overall survival of all 52 patients was 16.9 months (95% CI 13.1 to 25.2). 8 of 52 were alive at the end of the study.
  • In multivariate analysis, multimodality treatment including surgery (HR 0.347, CI 0.13 to 0.90, p = 0.029) and stage (HR 4.989 for late stage, CI 1.64 to 15.13, p = 0.005) were independent prognostic factors for overall survival.
  • All patients: median survival was 15.3 months (11.5 to 24.4) with PD-L1 TPS of 1% or more versus 20.0 months (11.2 to 34.9) below 1% (p = 0.364). In multivariate analysis PD-L1 was not an independent factor (HR 1.366, CI 0.54 to 3.46, p = 0.511).
  • All patients: median survival was 20 months (15.2 to 28.1) with BAP-1 loss versus 11.3 months (5.6 to 31.0) for BAP-1-positive patients (p = 0.153).
  • In the 27 patients treated with multimodality treatment including surgery, median survival was 15.8 months with PD-L1 TPS of 1% or more versus 31.3 months in PD-L1-negative patients (p = 0.053).
  • ILK expression of 50% or more was not significantly associated with survival: median 16.9 months for ILK of 50% or more versus 15.8 months below 50% (univariate p = 0.134). The multivariate result was also not significant (HR 0.874, CI 0.24 to 3.14, p = 0.837).
  • Combinations of PD-L1 positivity with BAP-1 positivity (CPS: p = 0.045; TPS: p = 0.059) or with ILK of 50% or more (CPS: p = 0.019; TPS: p = 0.023) were associated with worse survival.
  • The 12 patients who received immunotherapy at some point had median survival of 24.0 versus 15.2 months. No p-value was given.
• The authors' conclusion: The authors concluded that their exploratory analysis showed high rates of PD-L1, BAP-1 and ILK expression, that patients with PD-L1 expression had survival disadvantages, and that treatment decisions might be individualized based on biomarker patterns.
• Limitations the authors state:
  • The study was retrospective, and the number of patients was limited because the disease is rare.
  • Over the long study period, patients received many different treatments.
  • The combined-marker results should be interpreted with caution because of the small sample size.
  • In the surgery subgroup, few patients were BAP-1-positive and the confidence interval was large.

Topics

Medical terms in this study, explained in our Lexicon: PD-L1, Pleural Mesothelioma, Prognosis, Biomarker, Non-epithelioid, Median Overall Survival, Multimodal Therapy.

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